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CC BY 4.0 · Arq Neuropsiquiatr 2025; 83(05): s00451804922
DOI: 10.1055/s-0045-1804922
Original Article

Association among blood pressure, antihypertensive drugs, and amyotrophic lateral sclerosis

Zhiguang Li 
1   Xingtai Central Hospital, Department of Neurology, Xingtai Hebei, People's Republic of China.
2   Xingtai Medical College, Department of Basic Medicine, Xingtai Hebei, People's Republic of China.
,
Yan Li 
1   Xingtai Central Hospital, Department of Neurology, Xingtai Hebei, People's Republic of China.
,
Jiankai Zhao 
1   Xingtai Central Hospital, Department of Neurology, Xingtai Hebei, People's Republic of China.
2   Xingtai Medical College, Department of Basic Medicine, Xingtai Hebei, People's Republic of China.
,
Feifei Zhang 
2   Xingtai Medical College, Department of Basic Medicine, Xingtai Hebei, People's Republic of China.
,
Wei Dang 
2   Xingtai Medical College, Department of Basic Medicine, Xingtai Hebei, People's Republic of China.
,
Yanan Jia 
3   Xingtai Central Hospital, Department of Science and Education, Xingtai Hebei, People's Republic of China.
,
Fei Guo 
2   Xingtai Medical College, Department of Basic Medicine, Xingtai Hebei, People's Republic of China.
,
Lixin Guo 
2   Xingtai Medical College, Department of Basic Medicine, Xingtai Hebei, People's Republic of China.
4   Xingtai Central Hospital, Department of Cardiac Surgery, Xingtai Hebei, People's Republic of China.
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Abstract

Background Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. The impacts of antihypertensive drugs and blood pressure (BP) on ALS are currently debatable.

Objective To evaluate the causal relationship involving antihypertensive drugs, BP, and ALS through a Mendelian randomization (MR) analysis.

Methods The causal relationship between BP and ALS was evaluated by a bidirectional two-sample MR analysis. Then, a sensitivity analysis was performed using a secondary BP genome-wide association study. The drug-target MR was employed to evaluate the impact of antihypertensive drugs on ALS. Furthermore, we used cis-expression quantitative trait loci (cis-eQTLs) data from brain tissue and blood to validate the positive results by a summary-based MR method.

Results We found that an increment in systolic BP (SBP) could elevate the risk of ALS (inverse-variance weighted [IVW] odds ratio [OR] = 1.003; 95% confidence interval [95%CI]: 1.001–1.006; per 10-mmHg increment) and ALS might be protected by angiotensin-converting enzyme inhibitors (ACEIs; OR = 0.970; 95%CI: 0.956–0.984; p = 1.96 × 10−5; per 10-mmHg decrement). A causal relationship was not observed between diastolic BP and other antihypertensive drugs in ALS.

Conclusion In the present study, genetic support for elevated SBP serves as a risk factor for ALS. Besides, ACEIs hold promise as a candidate for ALS.

Keywords

Blood Pressure - Antihypertensive Agents - Mendelian Randomization Analysis - Amyotrophic Lateral Sclerosis

Ethics Approval

All data used in the present study was from publicly available summary-level data from GWAS and expression quantitative trait loci (eQTLs) studies and the ethical approval included can be found in the original articles.


Data Availability Statement

The summary statistics used in the current study are available from the corresponding author upon reasonable request.


Authors' Contributions

ZGL, FG: conceptualization; ZGL, YL, JKZ: methodology; ZGL, WD: software; ZGL, FG: validation; YNJ: formal analysis, investigation; ZGL: resources; FFZ: data curation; ZGL: writing—original draft preparation; ZGL, YL: writing—review and editing; ZGL: visualization; LXG: supervision, project administration. All authors have read and agreed to the published version of the manuscript.


Editor-in-Chief: Hélio A. G. Teive.


Associate Editor: Paulo José Lorenzoni.




Publication History

Received: 29 March 2024

Accepted: 12 November 2024

Article published online:
13 May 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Zhiguang Li, Yan Li, Jiankai Zhao, Feifei Zhang, Wei Dang, Yanan Jia, Fei Guo, Lixin Guo. Association among blood pressure, antihypertensive drugs, and amyotrophic lateral sclerosis. Arq Neuropsiquiatr 2025; 83: s00451804922.
DOI: 10.1055/s-0045-1804922
 

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